Phosphate backbone epitranscriptomics: Discovery of natural RNA phosphorothioates and their writer machinery.

Natural RNA phosphorothioates and their enzymatic machinery are identified across diverse archaeal species, marking the first discovery of phosphate-backbone modifications in RNA.

• Why it matters: Understanding RNA modifications is crucial because they influence RNA stability and function, yet no natural modifications on the phosphate backbone have been known, leaving a significant gap in RNA biology.
• What they did: Researchers developed sequencing and mass spectrometry methods to map RNA phosphorothioates at single-nucleotide resolution and studied their regulation, enzyme families, and functional roles in archaea.
• The result: The study reveals that RNA PSs are dynamically regulated, enhance tRNA stability, and are produced by a specific enzyme family, providing a new foundation for exploring RNA modification mechanisms.